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Reciprocal intronic and exonic histone modification regions in humans

Nature Structural & Molecular Biology volume 17, pages 14951499 (2010) | Download Citation

Abstract

While much attention has been focused on chromatin at promoters and exons, human genes are mostly composed of intronic sequences. Analyzing published surveys of nucleosomes and 41 chromatin marks in humans, we identified histone modifications specifically associated with 5′ intronic sequences, distinguishable from promoter marks and bulk nucleosomes. These intronic marks were spatially reciprocal to trimethylated histone H3 Lys36 (H3K36me3), typically transitioning near internal exons. Several marks transitioned near bona fide exons, but not near nucleosomes at exon-like sequences. Therefore, we examined whether splicing affects histone marking. Even with considerable changes in regulated alternative splicing, histone marks were stable. Notably, these findings are consistent with exon definition influencing histone marks. In summary, we show that the location of many intragenic marks in humans can be distilled into a simple organizing principle: association with 5′ intronic or 3′ exonic regions.

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Acknowledgements

We thank the following for kindly providing reagents and data: S. Oberdoerffer and A. Rao (Harvard Medical School) for B-cell lines, N. Spies and C. Burge (MIT) for ECR locations, and E. Shema and M. Oren (Weizmann Institute of Science) for H2Bub ChIP-seq data. We also thank H. Madhani and J. Steitz for critical reading of the manuscript and the Guthrie, Yamamoto and Panning groups for helpful discussions. J.T.H. and A.M.P. were supported by individual ARCS Foundation Scholarships. Research support was provided by US National Institutes of Health grants GM21119 to C.G. and CA020535 to K.R.Y. C.G. is an American Cancer Society Research Professor of Molecular Genetics, and K.R.Y. is a consultant with Merck & Co.

Author information

Author notes

    • Jason T Huff
    •  & Alex M Plocik

    These authors contributed equally to this work.

Affiliations

  1. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA.

    • Jason T Huff
    •  & Keith R Yamamoto
  2. Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.

    • Alex M Plocik
    •  & Christine Guthrie

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Contributions

J.T.H. and A.M.P. designed and performed the analyses and experiments. J.T.H., A.M.P., C.G. and K.R.Y. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Christine Guthrie or Keith R Yamamoto.

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DOI

https://doi.org/10.1038/nsmb.1924

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